Original Article

Impact of Measles Vaccination on the Acquisition and Frequency of

Measles Infection in Province of Sindh

Ammarah Jamal1, Yousuf Yahya2, Agha Muhammad Ashfaq3, Zahoor Baloch4

Abstract

Objective: To determine the status of vaccination among confirmed measles cases and to determine
the association of vaccination status with the occurrence of measles infection.
Methods: A cross-sectional survey was carried out in the province of Sindh from January 2016 to April
2016. The study included patients of both gender, ≥ 9 months of age, fulfilling the case definition of
measles by World Health Organization (WHO), who were reported to and/or picked by the measles
surveillance officers. A sample of 3-5 ml of blood was collected from each registered patient between
day 4 and day 28 of the rash to test for measles IgM antibodies. The samples were labelled and
sent to National Measles Laboratory, National Institute of Health (NIH) Islamabad in reverse cold
chain. Patients who tested positive for IgM antibodies were grouped as confirmed measles while pa-
tients negative for measles IgM antibodies were grouped as suspected measles. Data of both the
groups was analysed using windows SPSS 21 for vaccination status, for frequency of measles infec-
tion against the number of doses of measles vaccine received. Frequencies of vaccination among
confirmed measles cases were compared with suspected measles for statistical significance using
Chi-square. P-value of <0.05 was taken as significant.
Results: A total of 572 out of 915 study subjects were confirmed measles cases, of which 258
(45%)were never vaccinated against the disease as compared to 72 (12.6%) who were completely
vaccinated. Overall, 128 (37.3%) were fully vaccinated amongst suspected measles. Vaccination sta-
tus was not known in a quarter of patients in both groups. A significant association was found be-
tween the vaccination status and measles infection with higher frequency of measles in unvaccinated
as compared to the vaccinated (p<0.001).
Conclusion: We conclude that the vaccination rate among measles patients was significantly lower
than among non-measles patients. A sizable 12.6% got the disease in spite of completing measles
vaccination.
Keywords: Measles, immunization, children, vaccine, MMR vaccine.
IRB: Approved by Institutional Review Board of Dow University of Health Sciences. Dated: 9th Septem-
ber 2017.
Citation: Jamal A, Yahya Y, Ashfaq AM, Baloch Z. Impact of Measles Vaccination on the Acquisition and
Frequency of Measles Infection in Province of Sindh. Annals ASH KM&DC 2017;22:237-42.
(ASH & KMDC 22(4):237;2017)

Introduction sible for 50-60% of the 1.6 million deaths occurring

globally each year caused by vaccine preventable
Measles is the most infectious disease known, diseases of childhood. Approximately 66% of these
affecting 30 million people annually and is associ- deaths occur in under-privileged countries including
ated with an infectivity rate of almost 100%1,2,3. It Pakistan in spite of the accessibility to an effective
not
________only
__________causes
_______________a
____lot
_______of
_____morbidity
___________________but
________is
_____respon-
_____________ vaccine3,4. The case fatality rate of measles may
1-2
Department of Paediatrics,
Dow University of Health Sciences, Civil Hospital, Karachi stretch up to 10% in regions afflicted with prevalent
3-4
EPI Program, Province of Sindh malnutrition and dearth of sufficient health facili-
Correspondence: Dr. Ammarah Jamal
Department of Paediatrics,
ties4. In the absence of any specific treatment
Dow University of Health Sciences, Civil Hospital measles vaccine remains the only option to protect
Email: drasjpk@yahoo.com
our children against this potentially fatal disease.
Date of Submission: 21st July 2017
Date of Acceptance: 5 th December 2017 The importance of vaccination is proven by the in-
237 Annals Abbasi Shaheed Hospital & Karachi Medical & Dental College
Ammarah Jamal, Yousuf Yahya, Agha Muhammad Ashfaq, Zahoor Baloch
terruption of endemic transmission of measles in
many countries having a high vaccine coverage with
consequent drop of 79% in measles deaths be-
tween 2000 and 20141,4,5. The situation in Pakistan
during those years was unfortunately contrary to
these countries. With reporting of 5969 lab con-
firmed cases in 2013 as compared to the 2676 con-
firmed cases in 2012 Pakistan stood out as the
highest measles reporting country in the Eastern
Mediterranean region6,7. This raises the question if
the measles vaccine is being administered at the
wrong time or not at all or is ineffective due to
some factors which need to be explored8. In Paki-
stan, measles vaccine used to be given as a single
dose at nine months of age9 but later, on recom-
mendation by World Health Organisation (WHO)
and United Nations International Children's Emer-
gency Fund (UNICEF), a booster dose at 15
months was introduced in Expanded Program on
Immunization (EPI) in 200910,11. Regarding the age
of vaccination, analysis of four months unpublished
records of a single paediatric unit of Civil Hospital
Karachi showed that 20 out of 100 children infected
with measles were below the age of first inoculation
against measles. The official estimate of measles
vaccine coverage in Pakistan revealed a disappoint-
ing coverage of 80% and 53% in 2012 with the 1st
and 2nd dose, respectively, while it was reported
63% in 201412. These two factors are strong
enough to explain the high surge in the measles
cases contrary to the rapid decline witnessed by
the rest of the world. But at the same time a study
conducted in Karachi, during a measles epidemic,
showed that 78% of the children had received at
least a single dose of measles vaccine. However,
the measles antibodies, which indicate immunity
against measles, were found in only 55% of the
children8. It was observed during the last few years
that an increasing number of patients who were
getting infected with measles had already received
vaccine against measles. We decided to determine
the frequency of measles cases that were already
immunised against the disease. We also deter-
mined the relationship between the number of
doses of measles vaccine received and the fre-
Volume No. 22 (4), December 2017
quency of infection and then will further analyse the
data to determine an association between the num-
bers of doses of measles vaccine received with
probability of acquiring measles infection by com-
paring the vaccination status in confirmed measles
cases with that of suspected measles. Once
shown that a substantial number of patients are
getting infected with measles in spite of being
immunised against the disease, we will move to
carry out large scale, multicentre study at a na-
tional level to assess the factors responsible for the
probable vaccine failure and take steps to remove
or modify those factors on urgent basis. This will go
a long way in decreasing a very high economic
loss, morbidity and, above all, mortality associated
with the disease.
Methods
A cross-sectional survey was carried out in the
province of Sindh over a period of four months from
January 2016 to April 2016. Sample size of 317
cases was calculated using the formula
n=(Z2P(1P))/e2 for average measles prevalence of
71%, with margin of error 5%, on 95% confidence
intervals. Although the minimum sample size re-
quired was 317, we increased the size to 915 to
cover up for the probable drop outs during the sur-
vey and to increase the reliability of results.The
study included all patients of both gender, ≥9
months of age, fulfilling the case definition of
measles suggested by WHO and who were re-
ported to and/or were picked by the measles sur-
veillance officers. Suspected measles case was
defined as 'any person with generalised maculo-
papular rash and fever plus one of the following:
cough or coryza (runny nose) or conjunctivitis (red
eyes)' or 'any person in whom a clinician suspects
measles'. Cases where information such as age,
vaccination status or epidemiology number (EPID
number) was missing were excluded from the study.
This survey was carried out as a part of
measles case-based surveillance and outbreak in-
vestigation EPI, province of Sindh. The surveillance
officers regularly visited or were called at the health
238
 Impact of Measles Vaccination on the Acquisition and Frequency of Measles Infection in Province of Sindh

facilities including all major tertiary care hospitals of Results

the province to identify and register all the patients
Case records of 1033 patients were analysed.
of suspected measles. Data was recorded on stan-
Out of these 915 fulfilled our criteria of being ≥ 9
dard, predesigned pro forma including age, gender,
months of age. 464 out of these were males
vaccination status, address and reporting institute.
amounting to 51% while the rest of the 49% were
Vaccination status was determined by vaccination
females. Serum IgM antibodies against measles
cards if available or by verbal information from the
came out positive in 572 (62.51%) out of the 915
parents. The data was then transferred to the line
and thus were confirmed as measles cases. Fig.1
list of the EPI Sindh on regular basis. A sample of
is showing the analysis of the study subjects as a
3-5 ml of blood was collected in sterile syringe from
flow chart. Analysis of vaccination status of these
each registered patient between day 4 and day 28
572 measles IgM positive cases showed decreasing
of the onset of rash to test for measles IgM anti-
frequency of measles infection with increasing num-
bodies as a confirmation of the diagnosis of
ber of doses of measles vaccine. A total of 258
measles. The samples were then labelled, allotted
(45%) of the patients who had measles were those
an EPID number and sent via EPI offices to Na-
who had never been vaccinated against the disease
tional Measles Laboratory, NIH Islamabad in reverse
as compared to 72 (12.6%) who had received both
cold chain with the maintenance of temperature be-
the doses of vaccine (Table 1). There is a large
tween 2-8oC. Patients who tested positive for IgM
group of 146 (25.5%) whose vaccination status was
antibodies in their blood were grouped as confirmed
not known. Vaccination status of ≥ 9 months old
measles cases while patients whose blood speci-
with measles IgM negative showed that 128
mens turned out to be negative for measles IgM an-
(37.3%) did not get measles were fully vaccinated
tibodies were grouped as suspected measles.
against the disease while 96 (28%) were never vac-
Since the age of first inoculation against measles in
cinated (Table 1). In this group also there were 70
our country is nine months, to comply with our ob-
(>20%) whose vaccination status was not known. A
jective, data of the subjects ≥9 months of age in
significant association was found between the vac-
both the groups was analysed using windows
cination status and the occurrence of measles in-
SPSS version 21 for their vaccination status in or-
fection with higher frequency of measles detected
der to determine the frequency of patients who de-
in unvaccinated subjects as compared to the vac-
veloped measles when they were unvaccinated,
cinated (p<0.001) (Table 2).
partially vaccinated or completely vaccinated. Fur-
ther analysis was done to determine the frequency
Discussion
of measles infection against the number of doses of
measles vaccine received. Finally the analysis was In our study, we could assess the
done to determine the association of measles vac- immunisation status in about 76% of all the pa-
cination with the occurrence of measles infection by tients who were initially recruited as measles. This
comparing the vaccination status of the confirmed frequency is comparable to or even better than
measles cases with that of suspected measles. those of several other countries including the well-
Statistical significance was checked by using Chi- developed ones. Studies from Ontario/Canada and
square. P-value of <0.05 was taken as significant. Malaysia were able to gauge the immunisation sta-
tus of their measles patients in 70%13 and 69%14,
Other results including gender, IgM serology
respectively. The rate of the evaluation of the
and status of vaccination were described in frequen-
immunisation status was even lower in
cies and percentages.
Mozambique and California/USA ranging from 29%-
43%15. The highest numbers of vaccination records
available for 95% of the cases were reported from

239 Annals Abbasi Shaheed Hospital & Karachi Medical & Dental College
Ammarah Jamal, Yousuf Yahya, Agha Muhammad Ashfaq, Zahoor Baloch

Table 1. Vaccination status among ≥9 months of age with confirmed Table 2. Association of vaccination status with frequency of measles
and suspected measles (n= 915) infection (n= 699)

No. of doses of Children with measles Children with measles Vaccination Number of Measles (IgM) Measles (IgM) p-value
vaccine received IgM positive, n (%) IgM negative, n (%) status patients positive, n (%) negative, n (%)

Two doses 72 (12.60) 128 (37.30) vaccinated 345 168 (48.7) 177 (51.3)
One dose 96 (16.80) 49 (14.30) Non vaccinated 354 258 (72.9) 96 (27.1) <0.001*
None 258 (45.10) 96 (28.00) Total 699 426 (60.94) 273 (39.05)
Status not known 146 (25.50) 70 (20.40)
Total 572 (100) 343 (100) Chi-square test used for association

Fig. 1. Flow chart showing the analysis of study subjects

European Union (EU) & European Economic Area
(EEA) countries16. This availability of the records re-
flects on the health awareness and education of the
parents and the efficacy of their health and
immunisation departments. The frequency of the
records available in our series is unexpectedly high
though it may not represent the true rate as a lot of
patients may not have reported to the surveillance
officers. Analysis of the vaccination status of con-
firmed measles cases in our study revealed that
Volume No. 22 (4), December 2017
45% were never vaccinated against measles. The
frequency of unvaccinated among measles is simi-
larly and globally high varying from 45%-83% as re-
ported from California, Canada13, Mozambique15 and
EU/EEA countries16. USA reported that 63 out of 64
reported measles cases in one analysis were
unimmunised. On the other hand in Malaysia
31.29% were not vaccinated14. This high frequency
of unvaccinated in measles suggest a protective
role of measles vaccine against the disease. To
240
 Impact of Measles Vaccination on the Acquisition and Frequency of Measles Infection in Province of Sindh
confirm this positive correlation between the ab-
sences of vaccination with higher frequency of
measles infection we compared the frequency of
measles cases among unvaccinated with the fre-
quency of measles among those who have received
one or two doses of the vaccine and it turned out
that increasing number of doses was associated
with decreased frequency of measles infection. That
is only 12.6% of the children who had received both
doses of measles vaccines were affected by the
disease as against 45% among those who received
nil doses. One important fact that came up in this
study is that an overall 30% of the cases got the
measles even though they had received at least
one dose of the vaccine against the disease. This
included a little over 12% of patients who had re-
ceived both the doses of the vaccine. These results
of measles infection in the vaccinated population
are again comparable to the reported frequency
range of 9%-30% from other regions including
Canada13, California, EU/EEA countries16 and Ma-
laysia14, This is inclusive of 1.8%-15% who had had
their complete series of inoculation against
measles. The proportion of unvaccinated cases was
high among all age groups16. Pennsylvania and Vir-
ginia reported measles infection during an outbreak
in 2009 in two physicians both of whom have been
fully vaccinated against the disease17. This occur-
rence of measles infection in the vaccinated indi-
viduals rang the alarm bells about the efficacy of
the vaccine and provides enough grounds to explore
the reason for such phenomenon. Some of the
studies done so far in this regard has shown re-
duced formation of IgG antibodies in response to
measles vaccination in under developed countries
including Pakistan where the seroconversion was
reported in only 73.8% of the children vaccinated
against the disease18. One positive observation
made during the infection of the two American phy-
sicians was the absence of spread of the infection
to others thus suggesting a very low infectivity po-
tential as compared to fully symptomatic individu-
als17. While we need to check into the causes of
measles infection in immunised individuals before it
is too late, the more significant food for thought and
241
action is a high number of children remaining un-
vaccinated. The answer may lie within the domain
of EPI including quality assurance of the informa-
tion and surveillance system, accuracy of demo-
graphic data used by the program to calculate
vaccination targets and vaccine coverage. In addi-
tion, it may also be affected by the availability of
human resources, will, equipment and the political
and professional commitment by the concerned per-
sonnel. It is extremely unfortunate that the province
of Sindh which contributes most to the measles in-
cidence and mortality is also a home to one of the
most corrupt health departments as has been de-
clared by the Transparency International19. The
study is limited by the fact that this data does not
include the patients who preferred private treatment
or to remain at home. Furthermore, lack of knowl-
edge of the vaccination status in almost quarter of
the patients may result in false interpretation of the
results although it can be presumed that absence
of knowledge means no vaccination. We recom-
mend that a strategy be devised and followed to in-
crease the routine vaccine coverage to >95%. We
also recommend that efforts be made to maintain
the vaccination records of all children. There is a
dire need to not only determine the factors respon-
sible for the poor vaccine coverage and records but
find a solution to the problems on urgent basis.
Above all there is a need to educate the public re-
garding the importance and safety of vaccination via
all means including media, mosques and school
health services. Last, but not the least, we recom-
mend large scale studies to determine the factors
associated with measles infection in those already
immunised against the disease.
Conclusion
We conclude that there is a significant asso-
ciation between the vaccination against measles
and acquisition of measles infection with higher fre-
quency of measles occurring in unvaccinated as
compared to the vaccinated. There is a sizable
12.6% who got the disease in spite of receiving
both the doses of measles vaccine. In approxi-
mately quarter of the patients, vaccination status
was not known.
Annals Abbasi Shaheed Hospital & Karachi Medical & Dental College
Ammarah Jamal, Yousuf Yahya, Agha Muhammad Ashfaq, Zahoor Baloch
Acknowledgements
We deeply acknowledge the support of Mr.
Syed Ejaz Alam (Statistical Officer, PHRC, Re-
search centre JPMC) and Dr. Syeda Kanwal (Senior
Surveillance Officer EPI Sindh) for their statistical
advices.
Conflict of Interest
Authors have no conflict of interests and no
grant/funding from any organisation for this study.
References
1. Mason WH. Measles. In: Kliegman RM, Stanton
BF, St Geme III JW, Schor NF, editors. Nelson
Textbook of Pediatrics. 20th ed. Philadelphia:
Elsevier Saunders; 2016. p. 1542-8.
2. Mehta P. The Measles Vaccine [Online]. Mehta
Childcare; 2016. Available from: http://
w w w. m e h t a c h i l d c a r e . c o m / v a c c i n e s / m e a s l e s
vaccine.htm. Accessed on November 18, 2017.
3. Rahim F, Habib-ur-Rehman and Afridi JM.
Measles- Demographic profile and complications
in children [Online]. J Med Sci 2011;19:174-6.
Available from: http://www.jmedsci.com/admin/
uploadpic/JMS-5-oct2011.pdf. Accessed on No-
vember 18, 2017.
4. WHO. Measles [Online]. Geneva: World Health Or-
ganization; 2016. Available from: http://who.int/
mediacentre/factsheets/fs286/en/. Accessed on
November 18, 2017.
5. Beach R, Thalange N. Infectious disease and im-
munity. In: Thalange N, Beach R, Booth D, Jack-
son L, editors. Essentials of Paediatrics. 2nd ed.
Philadelphia: Elsevier Saunders; 2013.p. 231-46.
6. WHO. Measles deaths decline, but elimination
progress stalls in some regions. Improved vacci-
nation rates critical for success [Online]. Geneva:
World Health Organization; 2013. Available from:
http://www.who.int/mediacentre/news/notes/2013/
measles_20130117/en/. Accessed on November
18, 2017.
7. WHO. Reported measles cases and incidence
rates by WHO Member States [Online]. Geneva:
World Health Organization; 2012. Available from:
http://www.who.int/immunization/
monitoring_surveillance/burden/vpd/
surveillance_type/active/measles_monthlydata/en/.
Accessed on November 18, 2017.
8. Niazi AK, Sadaf R. Measles epidemic in Pakistan:
In search of solutions. Ann Med Health Sci Res
2014;4:1-2. [DOI: 10.4103/2141-9248.126600].
9. Khan A, Ullah O, Ambreen, Ahmed I, Merajuddin.
Measles in vaccinated children 1.5 to 3 years of
age in rural community of district Peshawar, Paki-
stan. J Ayub Med Coll Abbottabad 2015;27:825-8
Volume No. 22 (4), December 2017
10. Rahman A, Saeed A, Ali M. Assessment of knowl-
edge and practices of mothers regarding
measles-2 immunization for children [Online]. Pak
J Med Health Sci 2013;7:719-21. Available from:
http://www.pjmhsonline.com/2013/july_sep/pdf/
719%20%. Accessed on November 18, 2017.
11. WHO. Response to measles outbreaks in
measles mortality reduction settings [Online].
Geneva: WHO Press; 2009. Available from: http://
www.who.int/immunization/documents/diseases/
measles_who_ivb_09_03/en/. Accessed on No-
vember 18, 2017.
12. Wasif S. Measles outbreak: The epidemic isn't
near; it's already here [Online]. Express Tribune;
2013. Available from: https://tribune.com.pk/story/
539790/measles-outbreak-the-epidemic-isnt-
near-its-already-here/. Accessed on November 18,
2017.
13. Lim GH, Deeks SL, Fediurek J, Gubbay J,
Crowcroft NS. Documenting the elimination of
measles, rubella and congenital rubella syn-
drome in Ontario: 2009-12 [Online]. CCDR; 2014.
Available from: https://www.canada.ca/en/public-
health/services/reports-publications/canada-com-
municable-disease-report-ccdr/monthly-issue/
2014-40/ccdr-volume-40-08-april-17. Accessed on
November 18, 2017.
14. WHO. Country Profile-Measles Elimination: Malay-
sia [Online]. Geneva: WHO press; 2016. Available
f r o m : h t t p : / / w w w. w p r o . w h o . i n t / i m m u n i z a t i o n /
documentsmeasles_country_profile_may2016_mys.pdf.
Accessed on November 18, 2017.
15. Jani JV, Jani IV, Araujo C, Sahay S, Barreto J,
Bjune G. Assessment of routine surveillance data
as a tool to investigate measles outbreaks in
Mozambique. BMC Infect Dis 2006;6:29. [DOI:
10.1186/1471-2334-6-29].
16. European Centre for Disease Prevention and
Control. Measles and rubella monitoring - March
2013: Surveillance Report [Online]. Stockholm;
2013. Available from: http://ecdc.europa.eu/en/
publications/Publications/measles-rubella-moni-
toring-report-march-2013. Accessed on November
18, 2017.
17. Rota JS, Hickman CJ, Sowers SB, Rota PA,
Mercader S, Bellini WJ. Two case studies of
modified measles in vaccinated physicians ex-
posed to primary measles cases: high risk of in-
fection but low risk of transmission. J Infect Dis
2011;204:S559-63. [DOI: 10.1093/infdis/jir098].
18. Zahoor MA, Rasool M H, Waseem M, Aslam B,
Zahoor MK, Saqalein M et al. Prevalence of
measles in vaccinated and non-vaccinated chil-
dren. EXCLI J 2015;14:504-7. [DOI: 10.17179/
excli2015-170].
19. Khan T, Qazi J. Measles outbreaks in Pakistan:
causes of the tragedy and future implications
[Online]. Epidemiol Rep 2014;2:1. Available from:
http://www.hoajonline.com/epidemiolrep/2054-
9911/2/1. Accessed on November 18, 2017.
242